New Research from the CWMH: Prenatal Supplement Containing Folate May Reduce Depressive Symptoms During Pregnancy

While there is research to support the reproductive safety of many antidepressants, many woman and their providers ask about alternatives to traditional antidepressants in women who are pregnant or planning to conceive. In a recent study, Dr. Marlene Freeman and colleagues at the Center for Women’s Mental Health explored the use of a folate-based preparation –EnBrace HR — for the prevention and treatment of depression in a group of pregnant women.

This research stems from data supporting a potential role for folate in the treatment of depression. Folic acid (or folate) is a B-vitamin needed for proper cell growth which is found in many food sources, such as lentils, dried beans and peas, and dark green vegetables. In addition, the FDA requires that all enriched cereal grains be fortified with folic acid. Nonetheless, some people are folate deficient or lack the enzyme (5,10-methylenetetrahydrofolate reductase or MTHFR) which converts folic acid to its active form, L-methylfolate.

Previous reports suggest that people with lower folate levels are at higher risk of major depression or may experience more severe depressive symptoms. Other studies indicate that in folate deficient patients, antidepressants may be less effective or may take longer to take effect. In addition, several clinical trials have shown that folic acid and related compounds (i.e., folinic acid and L-methylfolate) may reduce depressive symptoms, either when taken alone or in combination with an antidepressant.

In the current study, researchers recruited a group of women with histories of major depressive disorder (MDD) who were either pregnant (less than 28 weeks of gestation) or planning to conceive. This was an open-trial where participants received EnBrace-HR for 12 weeks. EnBrace-HR is a prescription prenatal supplement containing 5.53 mg L-methylfolate, 1 mg folic acid and 2.2 mg folinic acid.

At enrollment, women in Group 1 were euthymic (not depressed) and planned to discontinue antidepressants during pregnancy. The women in Group 2 were depressed. A diagnosis of MDD was confirmed using the Mini-International Neuropsychiatric Interview, and the severity of depressive symptoms was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS).

Group 1 participants (N = 11) experienced lower rates of depressive relapse (27.3%; P = .005) than what would be expected in women who discontinue antidepressants during pregnancy. If we compare this to data from a previous study where we measured rates of relapse in women with histories of MDD, about 67.7% of those women relapsed after discontinuing antidepressant.

Group 2 participants (N = 6), who were depressed at the time of enrollment, experienced significant improvements in the severity of depressive symptoms. Five of the women (83.3%) experienced an improvement in depression of > 50%, and one improved by 33.3%. One adverse event was reported, a hospitalization for depression.

This pilot study suggests that EnBrace HR may be helpful for not only for preventing depressive relapse during pregnancy but may also have antidepressant effects. Larger studies are required to better understand which women are likely to benefit from this intervention. While this was a small study, these results are exciting and we look forward to seeing more studies with EnBrace HR and similar compounds for women who are at risk for depression during pregnancy.